Condition category
Mental and Behavioural Disorders
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Eugenia Oviedo-Joekes


Contact details

School of Population and Public Health
University of British Columbia
Centre for Health Evaluation & Outcome Sciences
St. Paul's Hospital
620-1081 Burrard Street
V6Z 1Y6
+1 604 682 2344 Ext 62973

Additional identifiers

EudraCT number

2005-002896-33 number

Protocol/serial number


Study information

Scientific title

Efficacy of prescribed injected diacetylmorphine in the Andalusian trial: responders and non-responders evaluated using a multi-domain outcome index



Study hypothesis

The impact of intravenous diacetylmorphine (DAM) plus oral methadone is better than a treatment with oral methadone alone on the physical and mental health and social integration of refractory opioid addicts.

Ethics approval

Ethics board of the Hospital Virgen de las Nieves, approved on 01/08/2001 (ref: 01/15.2)

Study design

Open randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Refractory opioid addicts


Participants in the experimental group received DAM (heroin) injection twice a day, plus oral methadone once a day (to be taken at home) for 9 months. The control group received only oral methadone to be taken once a day.

The two groups received an equivalent opioid dose. Among treatment completers, an average DAM dosage of 274.5 mg/day (range: 15-600 mg) and an average methadone dosage of 42.6 mg/day (range 18-124 mg) were prescribed for the experimental group. The daily methadone dosage in the control group was 105 mg/day (range: 40-180 mg).

As a result, the approximate mean daily total equivalent dosage of DAM/day for the experimental group was between 395.5 and 414.5 mg/day; for the control group, it was between 361 and 400 mg/day.

Of the 62 participants, 44 completed the treatment and 50 patients were analysed.

Contact details of Principal Investigator:
Dr Joan Carles March
Andalusian School of Public Health (EASP)
18014, Spain
Tel: +34 958 027 400

Intervention type



Not Applicable

Drug names

Diacetylmorphine (DAM; heroin), methadone

Primary outcome measure

A dichotomous multidimension outcome (MDO) index was determined by protocol as a primary outcome variable, imputing success when the patient showed at least 20% improvement at 9 months, compared with the baseline values, in general health or psychological or family adjustment, without a deterioration superior to 20% in any of these dimensions evaluated with the respective Addiction Severity Index (ASI) composite scores.

Secondary outcome measures

The following were assessed before randomisation, at 3, 6 and 9 months (end of the trial):
1. Physical and mental health, assessed by the Opiate Treatment Index (OTI), Symptom Checklist (SCL) and Maudsley Addiction Profile (MAP)
2. Psychosocial adjustment, assessed by the OTI and ASI
3. Treatment retention
4. Illegal activities, assessed by the ASI
5. Illicit drug use, assessed by the OTI and ASI
6. Quality of life, assessed by the Health Related Quality of Life 12-item Short Form (SF-12)

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Both males and females, 21 years or older
2. Long-term opioid-dependent persons who had not been benefited from other treatments

Potential participants were interviewed in squares, soup kitchens and methadone dispensaries by outreach workers and peers, who suggested they make an appointment with a PEPSA physician.

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Non-agreement to participate
2. Psycho-social impairment to answer the questionnaires
3. Current medical, social or legal situation that is likely to result in an discontinuation period longer than the study period (9 months)

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

School of Population and Public Health
Vancouver, BC
V6Z 1Y6

Sponsor information


Drug Commission, Council for Equality and Social Welfare (Spain)

Sponsor details

C/o Andrés Estrada Moreno
Director General para las Drogodependencias y Adicciones
Consejería para la Igualdad y Bienestar Social
Junta de Andalucia
Avenida de Hytasa
+34 955 048 000

Sponsor type




Funder type


Funder name

Committee on Drug Dependence, Carlos III Health Institute (Spain)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

1. 2004 protocol in
2. 2006 main results:
3. 2007 review including data from this trial in
4. 2008 results in
5. 2009 results in
2008 results, comparing the baseline data from Canadian sample with the European trials, including the data from this trial:

Publication citations

  1. Results

    Perea-Milla E, Ayçaguer LC, Cerdà JC, Saiz FG, Rivas-Ruiz F, Danet A, Vallecillo MR, Oviedo-Joekes E, Efficacy of prescribed injectable diacetylmorphine in the Andalusian trial: Bayesian analysis of responders and non-responders according to a multi domain outcome index., Trials, 2009, 10, 70, doi: 10.1186/1745-6215-10-70.

  2. March JC, Oviedo-Joekes E, Romero M, Gómez M, Rodríguez S, León MI, Rodríguez C, , [The experimental drug prescription program in Andalusia [PEPSA]: procedure for recruiting participants]., Gac Sanit, 18, 3, 245-247.

  3. March JC, Oviedo-Joekes E, Perea-Milla E, Carrasco F, , Controlled trial of prescribed heroin in the treatment of opioid addiction., J Subst Abuse Treat, 2006, 31, 2, 203-211, doi: 10.1016/j.jsat.2006.04.007.

  4. Fischer B, Oviedo-Joekes E, Blanken P, Haasen C, Rehm J, Schechter MT, Strang J, van den Brink W, Heroin-assisted treatment (HAT) a decade later: a brief update on science and politics., J Urban Health, 2007, 84, 4, 552-562, doi: 10.1007/s11524-007-9198-y.

  5. de Arcos FA, Verdejo García A, López Jiménez A, Montañez Pareja M, Gómez Juárez E, Arráez Sánchez F, Pérez García M, [Emotional response to affective stimuli in subjects addicted to opiates engaged in controlled use as part of the P.E.P.S.A]., Adicciones, 2008, 20, 1, 27-35.

  6. Oviedo-Joekes E, Nosyk B, Brissette S, Chettiar J, Schneeberger P, Marsh DC, Krausz M, Anis A, Schechter MT, The North American Opiate Medication Initiative (NAOMI): profile of participants in North America's first trial of heroin-assisted treatment., J Urban Health, 2008, 85, 6, 812-825, doi: 10.1007/s11524-008-9312-9.

Additional files

Editorial Notes